DESCRIPTION (provided by investigator): Early-life experiences have profound effects on an individual's health. Physical and/or emotional abuse can lead to a negative sense of well-being, including behavioral problems that continue throughout life. It is estimated that youngsters and adults with history of physical and/or emotional neglect are likely to develop substance abuse, anxiety, and major depression. Though the emotional cost cannot be measured, the economic cost to society is estimated at $96 billion/year. While the mechanisms of stress response have been largely characterized in adults, little is known about the neurobiological consequences of early-life physical or emotional stress and its long-term consequences. These observations underscore the need for better understanding of the neurobiology of early-life stress and its life-long effects. The goal of this proposal is to study the role of brain's appetitive neural circuits in the long-term behavioral and biochemical consequences of stress, using a rodent model of physical (mild foot shock) versus emotional (witness foot shock) stress. This approach is novel because it focuses on appetitive regions of the brain (the nucleus accumbens and the VTA) important for motivation, reward, and psychomotor activity. Aim 1 examines whether exposure to physical or emotional stress during the life-span influences emotional reactivity using behavioral tests designed to assess an animal's affective state, these include assessing sensitivity to: (a) drugs of abuse (cocaine, morphine), (b) natural rewards (sucrose), and (c) reactivity to anxiety-eliciting situations (open-field), and other stressors (forced swim stress). Aim 2 assesses the biochemical integrity of this circuit, using protein biochemistry, after physical/emotional stress. This will allow for identification of gene products regulated by either form of stress, and by age, thus setting the stage for future experiments in which these identified 'stress- related'proteins will be packaged into viral vectors to study how they affect developing brain, resulting in adaptations that increase vulnerability to drugs of abuse and other behavioral disorders. Data obtained will improve our understanding of the role physical and emotional stress plays in early development in mediating pathological behavior later in life. PUBLIC HEALTH RELEVANCE: Youngsters and adults with childhood history of physical and/or emotional neglect are likely to develop substance abuse, anxiety, and major depression disorders. Though the economic cost to society is estimated at $96 billion/year, little is known about the neurobiological consequences of early-life physical or emotional stress and its long-term consequences. These observations underscore the need for better understanding of the neurobiology of early-life stress and its life-long effects.